Effect of Bone Marrow‐Derived Mesenchymal Stem Cells on Cochlear Function in an Experimental Rat Model

Abstract

Mesenchymal stem cell (MSC) therapy is an emerging treatment modality for various human diseases. Although induced pluripotent stem cells have been explored for the restoration of hearing, the potential of MSCs as a therapeutic strategy for various cochlear insults is not precisely known. MSCs possess anti‐inflammatory, anti‐apoptotic and neuroprotective properties, making them an attractive target for the treatment of inner ear disorders such as hair cell damage in response to inflammation. Most of the previous studies have used immunosuppression or the complex surgical techniques to deliver stem cells into the cochlea. However, no information is available regarding the biocompatibility and safety of MSCs in the inner ear in immunocompetent cochlea. The aim of the present study was to determine the effect of non‐surgical administration of rodent bone marrow derived MSCs (BM‐MSCs) through transtympanic delivery on the cochlear function and to assess any adverse effects on the auditory system employing a rat model without immunosuppression. We observed that the transtympanic administration of BM‐MSCs has no significant effect on the hearing thresholds as determined by auditory brainstem response and distortion product otoacoustic emissions. Histopathological examination revealed no recruitment of inflammatory leukocytes and edema in the cochlea of BM‐MSCs administrated rats. The results of this study suggest that transtympanic administration of BM‐MSCs is safe and can be explored in providing otoprotection against cochlear insults. Anat Rec, 303:487–493, 2020. © 2019 American Association for Anatomy

Application of Mesenchymal Stem Cell Therapy and Inner Ear Regeneration for Hearing Loss: A Review

“…The transtympanic administration of BM-MSCs has no significant effect on the hearing thresholds, as determined based on ABR and distortion product otoacoustic emissions (DPOAE), which can be used to measure outer hair cell function. Histopathological examination did not reveal recruitment of inflammatory leukocytes and edema in the cochlea of MSCs administered in rats [67].…”

Achievements and Challenges in Transplantation of Mesenchymal Stem Cells in Otorhinolaryngology

“…In mice, BMSCs were shown to enhance the regeneration and maintenance of fibrocytes in damaged SLs, leading to partial restoration of cochlear function [81]. Transtym-panic transplantation of rodent BMSCs in a non-immunocompromised rat model to assess cochlear function by ABR, distortion product otoacoustic emissions (DPOAE), and histopathology did not reveal the recruitment of inflammatory leukocytes and edema in the cochlea of MSCs administered rats [82]. Fetoni et al, in a noise deafened adult Guinea pig, found that transplanted AdSCs into scala tympani, via round window, were able to survive and migrate, at the site of tissue damage, and express trophic factors to pave the way for further treatment of deafness [83].…”

Progress in Modeling and Targeting Inner Ear Disorders with Pluripotent Stem Cells

“…In contrast, PSCs (embryonic stem cells [ESCs] and induced pluripotent stem cells [iPSCs]) have infinite self-renewal capacity and the ability to differentiate into any cell type of the three major germ layers. Somatic stem cells, such as mesenchymal stem cells and neural stem cells, have been used to generate inner ear progenitors and restore damaged spiral ganglia ( Boddy et al., 2012 , Mittal et al., 2020 , Xu et al., 2016 ). However, there are a limited number of sources for these somatic stem cells and they exhibit a restricted capacity for differentiation ( Clevers, 2015 ).…”